10-(2-Propynyl)-estr-4-ene-3,17-dione, described in U.S. Pat. No. 4,322,416, is a useful potent and selective aromatase inhibitor. In that patent, this compound is prepared by a multi-step procedure which comprises reacting the chloroethenyl compound, 3,3,17,17-bis(ethylenedioxy)-10-(3-chloro-prop-2-enyl)estr-5-ene, with a strong base in an inert solvent to yield the corresponding 10-(2-propynyl) compound, followed by treatment with acid to remove the protecting groups at the 3- and 17- positions, with shifting of any 5-unsaturation to the 4-position. This method of preparation is long, involves the use of mercury and lead, and requires chromatography. Although each step in this process proceeds in over 70% yield, the overall yield is only 13%.
More recently, Bednarski et al., J. Med. Chem., Vol 32, 203 No. 1 (1989), described a process for the preparation of 10-(2-propynyl)-estr-4-ene-3,17-dione. That process utilizes the preparation of ethylene ketal intermediates, but these and subsequent intermediates tend to oil out of recrystallization media and are difficult to handle in a process. In addition, although Bednarski did not recognize this fact, in the preparation of the initial bisketal, isomerization of the 5(10)-double bond occurs under the conditions described and the product obtained is actually a mixture of the product with a significant amount of an isomeric compound.